Toxic Effects of the Organophosphorus Insecticide Fenthion on Growth and Chlorophyll Production Activity of Unicellular Marine Microalgae Tetraselmis suecica: Comparison between Observed and Predicted Endpoint Toxicity Data

This chapter provides the results of a laboratory ecotoxicological study conducted to assess the acute toxicity of the organophosphorus pesticide fenthion toward the marine microalgal species Tetraselmis suecica. Bioassays were performed, and algal densities and chlorophyll pigments fractions were measured in the exponential phase after 96 h of exposure to fenthion. Two quantitative structure activity relationships (QSARs) were used to estimate the toxicity of 13 primary metabolites and degradation products of fenthion toward the selected organism; the first was based on the use of the n-octanol/water partition coefficient, whereas the second was based on the solubility of the compound in water. Results revealed that fenthion can have marked effects on the growth and photosynthesis of the target primary producers of marine ecosystems T. suecica. The parent pesticide toxicant was found not toxic to the tested algal species up to 1.00 mg L−1, while higher treatment concentrations not only affected algal densities and significantly decreased specific growth rate values (μ) (p < 0.05) but also decreased the contents of photosynthetic pigments. The comparison between the observed and the predicted toxicity values of the parent compound fenthion indicated that the predictive capability of the QSARs applied can be considered highly satisfactory. Consequently, both QSAR models were used for the prediction of toxicity data of fenthion’s principal metabolites and degradation products

Investigating the entire course of telithromycin binding to Escherichia coli ribosomes

Applying kinetics and footprinting analysis, we show that telithromycin, a ketolide antibiotic, binds to Escherichia coli ribosomes in a two-step process. During the first, rapidly equilibrated step, telithromycin binds to a low-affinity site (KT = 500 nM), in which the lactone ring is positioned at the upper portion of the peptide exit tunnel, while the alkyl–aryl side chain of the drug inserts a groove formed by nucleotides A789 and U790 of 23S rRNA. During the second step, telithromycin shifts slowly to a high-affinity site (KT* = 8.33 nM), in which the lactone ring remains essentially at the same position, while the side chain interacts with the base pair U2609:A752 and the extended loop of protein L22. Consistently, mutations perturbing either the base pair U2609:A752 or the L22-loop hinder shifting of telithromycin to the final position, without affecting the initial step of binding. In contrast, mutation Lys63Glu in protein L4 placed on the opposite side of the tunnel, exerts only a minor effect on telithromycin binding. Polyamines disfavor both sequential steps of binding. Our data correlate well with recent crystallographic data and rationalize the changes in the accessibility of ribosomes to telithromycin in response to ribosomal mutations and ionic changes

Spatial variability of precipitation regimes over Turkey

Turkish annual precipitation regimes are analysed to provide large-scale perspective and redefine precipitation regions. Monthly total precipitation data are employed for 107 stations (1963–2002). Precipitation regime shape (seasonality) and magnitude (size) are classified using a novel multivariate methodology. Six shape and five magnitude classes are identified, which exhibit clear spatial structure. A composite (shape and magnitude) regime classification reveals dominant controls on spatial variability of precipitation. Intra-annual timing and magnitude of precipitation is highly variable due to seasonal shifts in Polar and Subtropical zones and physiographic factors. Nonetheless, the classification methodology is shown to be a powerful tool that identifies physically-interpretable precipitation regions: (1) coastal regimes for Marmara, coastal Aegean, Mediterranean and Black Sea; (2) transitional regimes in continental Aegean and Southeast Anatolia; and (3) inland regimes across central and Eastern Anatolia. This research has practical implications for understanding water resources, which are under ever growing pressure in Turkey

Requirements and validation of a prototype learning health system for clinical diagnosis

Introduction Diagnostic error is a major threat to patient safety in the context of family practice. The patient safety implications are severe for both patient and clinician. Traditional approaches to diagnostic decision support have lacked broad acceptance for a number of well-documented reasons: poor integration with electronic health records and clinician workflow, static evidence that lacks transparency and trust, and use of proprietary technical standards hindering wider interoperability. The learning health system (LHS) provides a suitable infrastructure for development of a new breed of learning decision support tools. These tools exploit the potential for appropriate use of the growing volumes of aggregated sources of electronic health records. Methods We describe the experiences of the TRANSFoRm project developing a diagnostic decision support infrastructure consistent with the wider goals of the LHS. We describe an architecture that is model driven, service oriented, constructed using open standards, and supports evidence derived from electronic sources of patient data. We describe the architecture and implementation of 2 critical aspects for a successful LHS: the model representation and translation of clinical evidence into effective practice and the generation of curated clinical evidence that can be used to populate those models, thus closing the LHS loop. Results/Conclusions Six core design requirements for implementing a diagnostic LHS are identified and successfully implemented as part of this research work. A number of significant technical and policy challenges are identified for the LHS community to consider, and these are discussed in the context of evaluating this work: medico-legal responsibility for generated diagnostic evidence, developing trust in the LHS (particularly important from the perspective of decision support), and constraints imposed by clinical terminologies on evidence generation

Preliminary results of high resolution paleoceanography and paleoclimatology during sapropel S1 deposition (South Limnos Basin, North Aegean Sea).

Οι παλαιοπεριβαλλοντικές συνθήκες κατά τη διάρκεια απόθεσης του σαπροπηλού S1 στο Βόρειο Αιγαίο (πυρήνας βαρύτητας Μ-4, μήκους 2,53 m, λεκάνης νότιας Λήμνου) προσδιορίζονται με βάση την ποσοτική ανάλυση μικροπαλαιοντολογικών (βενθονικά και πλαγκτονικά τρηματοφόρα) και γεωχημικών (OC, δ13Corg) δεικτών. Χαρακτηριστικό του πυρήνα Μ-4 είναι η μεγάλη εμφάνιση του S1 που φτάνει το πάχος των 96 cm. Η μελέτη κατέδειξε ότι, το κατώτερο σαπροπηλικό στρώμα S1a αποτέθηκε σε θερμότερες συνθήκες, εντονότερης δυσοξίας, σε σχέση με το ανώτερο σαπροπηλικό στρώμα S1b.. Αύξηση της παραγωγικότητας και καλύτερη διατήρηση του οργανικού υλικού πιστοποιήθηκαν στο κατώτερο τμήμα του S1. Η διακοπή των σαπροπηλικών συνθηκών στα 8,0 Ka BP που χαρακτηρίζεται κυρίως από την αύξηση της σχετικής συχνότητας των συμφυρματοπαγών μορφών των βενθονικών τρηματοφόρων υποστηρίζει συνθήκες υψηλής οξυγόνωσης του πυθμένα και εισροή γλυκών υδάτων.The paleoenviromental conditions during the depositional interval of sapropel S1 in the northeastern Aegean (gravity core M-4, length 2.53 m; south Limnos basin) are studied based on quantitative micropaleontological (benthic and planktonic foraminifera) and geochemical (OC, δ13Corg) analyses. Special feature of core M-4 is the thickness of S1 layer (96 cm). Our study points that sapropelic layer S1a has been deposited in more dysoxic and warmer conditions in respect to S1b. Both primary productivity and preservation of organic material are more intense during the lower part of S1. An interruption of the sapropelic conditions at 8.0 Ka BP which is mainly characterized by the increase of agglutinated foraminiferal forms confirms both higher oxygen bottom conditions and freshwater input

How strongly programmed is a strong programme building?: A comparative analysis of outpatient clinics in two hospitals

Buildings are traditionally classified in Space Syntax theory as either strongly or weakly programmed. According to this theory, social life in strong programme buildings follows rules and requirements of the organisation, while space usage in weak programme buildings is assumed to follow spatial configuration. However, in recent studies it has been argued that weak programme buildings can show aspects of strong programming, too. This paper aims at a more detailed description of different levels of programming by identifying a set of criteria to differentiate between weak and strong programme. This is derived from early Space Syntax theories as well as from more recent contributions. These criteria are then applied to outpatient clinics in two hospitals using findings from an in-depth study of space usage as evidence. The main hypothesis to be tested is whether the two hospitals show different levels of programming, or are simply strongly programmed, as traditionally assumed in Space Syntax theory. Three different categories of users - physicians, nurses and clerks were observed and their work activities and interaction networks investigated. Results show that none of the two hospitals show aspects of strong programming only, but rather change from strong to weak depending on the different criteria. Moreover, none of the two cases is consistently stronger programmed than the other suggesting that the same building as well as the same building type can show different degrees of programming. The study provides an elaborate analysis of programming in buildings and thus offers a starting point for a renewed debate on programme in order to devise ways of quantifying the level of programming of buildings in the future, which to date has only been done qualitatively. It suggests that other complex building types should be studied and added to the analysis. The paper enhances our current understanding of how space usage patterns in complex buildings evolve and contributes to the articulation of one of the key theoretical concepts in Space Syntax

Determination of the effect of collars containing 10% w/w imidacloprid and 4.5% w/w flumethrin (Seresto®) on the incidence of Leishmania and other canine vector-borne pathogen infections in Greece

Background: The objective of this field study was to assess the effect of treating a considerable portion of a dog population naturally exposed to canine vector-borne pathogens (CVBPs) in endemic areas with a 10% w/w imidacloprid/4.5% w/w flumethrin collar (Seresto®) on the transmission of CVBPs and the resulting incidence of infection. Methods: A total of 479 dogs from two sites were enrolled in the study. Collars were placed on all dogs continuously for 21 months, with replacement of the collar every 7 months. All dogs were examined, including body weight and blood/conjunctival swab collections, every 7 months. Serum samples were analysed for the presence of antibodies against Leishmania infantum, Ehrlichia canis and Anaplasma phagocytophilum. PCR assays were also performed on blood samples and conjunctival swab collected from the dogs for the presence of L. infantum, and on blood samples only for the presence of Ehrlichia spp. and Anaplasma spp. Sand flies were collected, identified to species level and molecularly tested for L. infantum throughout two vector activity seasons. Results: The results showed that the Seresto collar was safe with continuous use. At study inclusion, 419, 370 and 453 dogs tested negative for L. infantum, Ehrlichia spp. and Anaplasma spp., respectively (353 dogs tested negative for any pathogen). Overall, 90.2% of the dogs were protected from L. infantum infection on both sites combined. The entomological survey confirmed the presence of competent vectors of L. infantum at all monitored locations, namely the sand flies Phlebotomus neglectus and Phlebotomus tobbi, both of which are regarded as the most important competent vectors in the Mediterranean basin. All captured sand flies tested negative for L. infantum. Protection against ticks and fleas was high, with only two dogs showing a low number of ticks and seven dogs having low numbers of fleas at single evaluation time points. Across the entire study population, a number of dogs became infected with tick-transmitted pathogens, but prevention of transmission was 93% for E. canis and 87.2% for Anaplasma spp. when all cases from both sites were combined. Conclusions: The Seresto® (10% w/w imidacloprid/4.5% w/w flumethrin) collar significantly reduced the risk of CVBP transmission when compared to previously observed incidences of CVBP infections in two highly endemic areas under field conditions

What You Find Depends on How You Measure It: Reactivity of Response Scales Measuring Predecisional Information Distortion in Medical Diagnosis

“Predecisional information distortion” occurs when decision makers evaluate new information in a way that is biased towards their leading option. The phenomenon is well established, as is the method typically used to measure it, termed “stepwise evolution of preference” (SEP). An inadequacy of this method has recently come to the fore: it measures distortion as the total advantage afforded a leading option over its competitor, and therefore it cannot differentiate between distortion to strengthen a leading option (“proleader” distortion) and distortion to weaken a trailing option (“antitrailer” distortion). To address this, recent research introduced new response scales to SEP. We explore whether and how these new response scales might influence the very proleader and antitrailer processes that they were designed to capture (“reactivity”). We used the SEP method with concurrent verbal reporting: fifty family physicians verbalized their thoughts as they evaluated patient symptoms and signs (“cues”) in relation to two competing diagnostic hypotheses. Twenty-five physicians evaluated each cue using the response scale traditional to SEP (a single response scale, returning a single measure of distortion); the other twenty-five did so using the response scales introduced in recent studies (two separate response scales, returning two separate measures of distortion: proleader and antitrailer). We measured proleader and antitrailer processes in verbalizations, and compared verbalizations in the single-scale and separate-scales groups. Response scales did not appear to affect proleader processes: the two groups of physicians were equally likely to bolster their leading diagnosis verbally. Response scales did, however, appear to affect antitrailer processes: the two groups denigrated their trailing diagnosis verbally to differing degrees. Our findings suggest that the response scales used to measure information distortion might influence its constituent processes, limiting their generalizability across and beyond experimental studies

Serum microRNA array analysis identifies miR-140-3p, miR-33b-3p and miR-671-3p as potential osteoarthritis biomarkers involved in metabolic processes.

Background: MicroRNAs (miRNAs) in circulation have emerged as promising biomarkers. In this study, we aimed to identify a circulating miRNA signature for osteoarthritis (OA) patients and in combination with bioinformatics analysis to evaluate the utility of selected differentially expressed miRNAs in the serum as potential OA biomarkers. Methods: Serum samples were collected from 12 primary OA patients, and 12 healthy individuals were screened using the Agilent Human miRNA Microarray platform interrogating 2549 miRNAs. Receiver Operating Characteristic (ROC) curves were constructed to evaluate the diagnostic performance of the deregulated miRNAs. Expression levels of selected miRNAs were validated by quantitative real-time PCR (qRT-PCR) in all serum and in articular cartilage samples from OA patients (n = 12) and healthy individuals (n = 7). Bioinformatics analysis was used to investigate the involved pathways and target genes for the above miRNAs. Results: We identified 279 differentially expressed miRNAs in the serum of OA patients compared to controls. Two hundred and five miRNAs (73.5%) were upregulated and 74 (26.5%) downregulated. ROC analysis revealed that 77 miRNAs had area under the curve (AUC) > 0.8 and p < 0.05. Bioinformatics analysis in the 77 miRNAs revealed that their target genes were involved in multiple signaling pathways associated with OA, among which FoxO, mTOR, Wnt, pI3K/akt, TGF-β signaling pathways, ECM-receptor interaction, and fatty acid biosynthesis. qRT-PCR validation in seven selected out of the 77 miRNAs revealed 3 significantly downregulated miRNAs (hsa-miR-33b-3p, hsa-miR-671-3p, and hsa-miR-140-3p) in the serum of OA patients, which were in silico predicted to be enriched in pathways involved in metabolic processes. Target-gene analysis of hsa-miR-140-3p, hsa-miR-33b-3p, and hsa-miR-671-3p revealed that InsR and IGFR1 were common targets of all three miRNAs, highlighting their involvement in regulation of metabolic processes that contribute to OA pathology. Hsa-miR-140-3p and hsa-miR-671-3p expression levels were consistently downregulated in articular cartilage of OA patients compared to healthy individuals. Conclusions: A serum miRNA signature was established for the first time using high density resolution miR-arrays in OA patients. We identified a three-miRNA signature, hsa-miR-140-3p, hsa-miR-671-3p, and hsa-miR-33b-3p, in the serum of OA patients, predicted to regulate metabolic processes, which could serve as a potential biomarker for the evaluation of OA risk and progression.Peer reviewedFinal Published versio

Report of the Regional Coordination Meeting for the North Atlantic (RCM NA) 2015

The 12th RCM North Atlantic was held in Hamburg (Germany) 14-18 September 2015. The main purpose of the RCM is to coordinate the National Programmes (NP) of the Member States (MS) in the North Atlantic region. National Programmes for 2011-2013 have been rolled over for the period 2014-2016. Therefore, the main focus at this year was to improve regional data collection, analysis and storage and the evolution towards Regional Coordination Groups (RCG).The impact of the introduction of the landing obligation and preparations for its implementation was also discussed taking into account possible changes in scientific sampling schemes. The participation of four National Correspondents make possible to address National administration issues related to the oncoming EU MAP. A data call was launched by the chairs of the RCM NA, RCM Baltic and RCM NS&EA where MS were requested to upload data for 2014 in the regional database (RDB Fishframe) hosted by ICES. All MS except France and Northern Ireland complied with this request on landings and effort data. All MS except France uploaded sample data for 2014. French data were available for the meeting using a web base interface. Evaluation of the data call for submission data to the RDB revealed the numbers of species in landings and sample data and the numbers of metiers in effort data are in general data stable. RCM NA see big improvements in the work MS are doing regarding data calls coming from a situation where some countries didn´t provide any data to a new scenario where everyone is providing data; at the same time the overall quality has significantly improved, which is a large step forward. Regional data collection, analysis, storage and the evolution towards Regional Coordination Groups (RCG). Optimizing and harmonizing fisheries management across MS is dependent on improving regional coordination. The group discussed various needs and aspects relevant for facilitating future work of the RCM. Future tasks for the RCM don’t differ much from the current tasks. The discussion was focused on the structure of the RCGs, funding and short term needs to address tasks in an efficient way in the future. Regional coordination encompasses many different aspects, ranging from regional cooperation, sampling design, quality control procedures, data storage and analysis to the actual coordination, reporting and accountancy. Current task sharing and coordination procedures as well as future mechanisms are partially covered under the current MARE study 2014/19 (FISHPI). The project and its progress were presented to the group. The outcomes of this study will demonstrate future procedures based on case studies. As substantial effort and costs are involved to facilitate the process of regional coordination, the group highlighted the importance to access to budgets to cover these costs. Development of the RDB is also crucial for future work of the RCGs; funds are needed for the development. Additionally, RCM NA identified 4 supra regional topics where work can be done intersesionally in cooperation with the rest of RCMs: (1) Cost sharing of funding surveys; (2) Impact of landing obligation; (3) reviewing the ICES list of data needs ; and (4) review and follow up on RDB upload logs. Due to the importance to moving to a regional catch sampling scheme, an exercise was realised using the distribution of landings by harbour and fleet segment as a proxy of sampling frames that could hypothetically operate in a regional probability based design. The exercise was based on landing weight, for the simple reason that this was the only complete variable that was available for all the various national data sets. A regional sampling design can however be optimized in any number of ways (e.g. by landings value, by métier diversity, by species diversity, by number of fishing trips). The aims and aspirations of the end users need to be defined to ascertain which is most appropriate. It is one of the overriding advantages of a regional sampling design (as opposed to the aggregation of national designs) that the overall coverage can be set out to achieve regional goals. The RCM NA analyzed and discussed the main achievements of WKISCON2. It was clear that concurrent sampling at-sea is a long-established practice in most MS and that, where it was applied, concurrent sampling of fishing trips on-shore resulted in substantial increases in species collected without jeopardizing the main uses of data. Stock assessment and discard estimation and management are the major current uses of concurrent sampling data. Concurrent sampling has also been providing other benefits than its initial reason, such as advice to local, national and international authorities, research on MSFD descriptors, mixed fisheries and gear interactions and on mortality of rare species, data-poor stocks and PETS. It was clear that concurrent sampling being a statistically valid method for species selection which has proven to fulfil different end-users needs, implementation constraints hinder concurrent sampling on-shore. Thus, in order to meet end-users needs and to overcome the constraints that may arise from the implementation of concurrent sampling in some countries, particularly on-shore, RCM NA considers that different statistically sound approaches other than concurrent sampling must be developed to be tested in the field, so they may provide useful alternatives. Introduction of the landing obligation and its impact in the implementation in scientific sampling schemes. In terms of evaluating the impact of the introduction of the Landing Obligation (LO) regulation on data collection, there is only limited experience as the current implementation only covers Pelagic and Industrial fisheries in this region but MS have or are preparing for the implementation where they can. It is currently perceived that this year is a transition period for the pelagic fisheries and that these fisheries and control agencies are not fully implementing the LO (managing but not enforcing). As a result MS did not have a lot of comments on the current year and are in general preparing for next year. During the meeting it was decided to gather further information to address this issue by getting member states who were present to fill in a table on “Monitoring the impact of the landing obligation on data collection in the North Atlantic region” outlining the current state of play. This table could be considered as a live document which should be filled in year by year as the Landing Obligation is phased in. This table will then serve to provide an historical record as countries can document the changes year by year and will also provide guidance and act as a learning tool to all member states on how other countries are implementing the LO. National administrations The group discussed the proposal for task sharing and criteria for joint surveys. RCM NS&EA and RCM NA 2014 discussed a cost model for the present joint MS financed surveys and for future joint surveys. In addition to this model, the RCM NA 2015 highlighted that four categories of surveys should be considered in relation to task sharing and criteria for joint surveys. In the light of cost sharing, the group commented that the current DCF recast proposal refers to ‘exploitation of stocks’ rather than EU TAC or landings. Given the relative stability, EU TAC shares are the preferred basis for sharing costs. The exploitation of stocks shall be interpreted as EU-TAC share as a default. In specific cases, RCGs can in the future agree on different interpretation where needed and feasible. Fully agreement among the group was concerning to the engagement and participation of National Correspondent (NC) in this meeting. The future role of the NCs in the RCG context was discussed, indicating a formal role for the NCs in the RCG process to approve and agree on regional arrangements. However, the current recast of the DCF doesn’t include the formal involvement of the NCs in the coordination procedures and meetings. RCM NA highlights this as potentially problematic for the foreseen formal role of the NCs. Other items on the agenda were the consideration of the follow up of relevant recommendations made last years by Liaison Meeting and presentations and relevant development from ICES, EC and SC-RDB